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Nucleosomes in solution exist as a mixture of twist-defect states

Edayathumangalam, Rajeswari S. and Weyermann, Philipp and Dervan, Peter B. and Gottesfeld, Joel M. and Luger, Karolin (2005) Nucleosomes in solution exist as a mixture of twist-defect states. Journal of Molecular Biology, 345 (1). pp. 103-114. ISSN 0022-2836. doi:10.1016/j.jmb.2004.10.012.

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The 2.0 Å crystal structure of a nucleosome core particle in complex with a bivalent pyrrole-imidazole polyamide reveals that this “clamp” effectively crossbraces the two gyres of the DNA superhelix, thereby stabilizing the nucleosome against dissociation. Using X-ray crystallography and footprinting techniques, we show that the clamp preferentially binds nucleosomes over free DNA, and that nucleosomal DNA exists as a mixture of multiple twist-defect intermediates in solution. The nucleosomes exist in one of two different conformations in various crystal structures that trap twist-defect intermediates, even on a strong positioning sequence. Evidence has been obtained supporting the existence of twist-defect states in nucleosomal DNA in solution that are similar to those obtained in crystal structures. Our results also substantiate the idea that twist diffusion may represent an important means of altering the accessibility of nucleosomal DNA both in the presence and in the absence of ATP-dependent chromatin-remodelling enzymes.

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Dervan, Peter B.0000-0001-8852-7306
Additional Information:© 2004 Elsevier. Received 30 July 2004; received in revised form 29 September 2004; accepted 8 October 2004. We thank Kevin Sullivan for joining us in developing the original idea of the nucleosome clamp; Pamela Dyer for help with reagents; and all Luger laboratory members for help and discussion. We also thank Andrew Flaus for critical reading of the manuscript and for helpful suggestions. This work was supported by a grant supplement GM57148 from the US National Institutes of Health (NIH) to K.L., J.M.G., and P.B.D., and by NIH grant GM61909 to K.L.
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Subject Keywords:nucleosome core particle (NCP); pyrrole-imidazole polyamide (Py-Im PA) clamp; twist defect; twist diffusion; nucleosome dynamics
Issue or Number:1
Record Number:CaltechAUTHORS:20160509-114906839
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Official Citation:Rajeswari S. Edayathumangalam, Philipp Weyermann, Peter B. Dervan, Joel M. Gottesfeld, Karolin Luger, Nucleosomes in Solution Exist as a Mixture of Twist-defect States, Journal of Molecular Biology, Volume 345, Issue 1, 7 January 2005, Pages 103-114, ISSN 0022-2836, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:66764
Deposited By: Victoria Brennan
Deposited On:17 May 2016 22:19
Last Modified:11 Nov 2021 00:02

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